Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-06T09:15:44.733Z Has data issue: false hasContentIssue false

10 - Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and multiple myeloma

Published online by Cambridge University Press:  10 January 2011

S. Vincent Rajkumar
Affiliation:
Mayo Clinic College of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
Suzanne R. Hayman
Affiliation:
Mayo Clinic College of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
Susan O'Brien
Affiliation:
University of Texas/MD Anderson Cancer Center, Houston
Julie M. Vose
Affiliation:
University of Nebraska Medical Center, Omaha
Hagop M. Kantarjian
Affiliation:
University of Texas/MD Anderson Cancer Center, Houston
Get access

Summary

Introduction

The plasma cell dyscrasias are a diverse group of disorders characterized by the presence of a monoclonal plasma cell population in the bone marrow. The most common plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, smoldering myeloma (SMM), multiple myeloma (MM), primary (AL or immunoglobulin light chain) amyloidosis, and Waldenstrom's macroglobulinemia (WM) (Table 10.1). This chapter is focused on the pathogenesis, clinical features, diagnosis, and management of MGUS, SMM, and MM.

Laboratory testing for monoclonal proteins

Monoclonal immunoglobulins are commonly referred to as monoclonal proteins, M proteins, or paraproteins. The presence of an M protein is indicative of an underlying clonal plasma cell proliferative disorder, although further testing is required to distinguish among the various plasma cell disorders.

Serum protein electrophoresis and immunofixation

Agarose gel serum protein electrophoresis (SPEP) and serum immunofixation (IF) are the main methods of detection of serum M proteins (Figure 10.1a and b). M proteins appear as localized bands on SPEP. Although presence of a localized band on SPEP is suggestive of M protein, IF is necessary for confirmation as well as to determine the heavy- and light-chain classes of the M protein. In addition, serum IF is more sensitive than SPEP and can detect smaller amounts of M protein, and should therefore be performed whenever MM or a related disorder is suspected. The size of the M protein is measured using the SPEP; small M proteins < 1 g/dL on SPEP and M proteins that are apparent only on serum IF are considered “unmeasurable.”

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Kyle, RA, Rajkumar, SV. Monoclonal gammopathy of undetermined significance. Br J Haematol 2006;134:573–89.CrossRefGoogle ScholarPubMed
Katzmann, JA, Clark, RJ, Abraham, RS, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437–44.Google ScholarPubMed
Bradwell, AR, Carr-Smith, HD, Mead, GP, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361:489–91.CrossRefGoogle ScholarPubMed
Drayson, M, Tang, LX, Drew, R, et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97:2900–2.CrossRefGoogle ScholarPubMed
Lachmann, HJ, Gallimore, R, Gillmore, JD, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 2003;122:78–84.CrossRefGoogle ScholarPubMed
Abraham, RS, Clark, RJ, Bryant, SC, et al. Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. Clin Chem 2002;48:655–7.Google ScholarPubMed
Kyle, RA, Rajkumar, SV. Plasma cell disorders. In: Goldman, L, Ausiello, D, eds. Cecil Textbook of Medicine, 22nd edn. Philadelphia, W.B. Saunders. 2004; 1184–95.Google Scholar
Rajkumar, SV. MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management. Hematology (Am Soc Hematol Educ Program) 2005;340–5.Google ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Prevalence of monoclonal gammopathy of undetermined significance (MGUS) among Olmsted County, MN residents 50 years of age. Blood 2003;102:934a (A3476).Google Scholar
Landgren, O, Gridley, G, Turesson, I, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood 2006;107:904–6.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. A long-term study of prognosis of monoclonal gammopathy of undetermined significance. N Engl J Med 2002;346:564–9.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later.[see comment]. Mayo Clin Proc 2004;79:859–66.CrossRefGoogle Scholar
Kyle, RA. “Benign” monoclonal gammopathy–after 20 to 35 years of follow-up. Mayo Clin Proc 1993;68:26–36.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Kyle, RA, Therneau, TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (MGUS). Blood 2005;106:812–17.CrossRefGoogle Scholar
Jego, G, Bataille, R, Geffroy-Luseau, A, et al. Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Leukemia 2006;20:1130–7.CrossRefGoogle ScholarPubMed
Bohnhorst, J, Rasmussen, T, Moen, SH, et al. Toll-like receptors mediate proliferation and survival of multiple myeloma cells. Leukemia 2006;20:1138–44.CrossRefGoogle ScholarPubMed
Mantovani, A, Garlanda, C. Inflammation and multiple myeloma: the Toll connection. Leukemia 2006;20:937–8.CrossRefGoogle ScholarPubMed
Donk, NW, Lokhorst, HM, Bloem, AC. Growth factors and antiapoptotic signaling pathways in multiple myeloma. Leukemia 2005;19:2177–85.CrossRefGoogle ScholarPubMed
Perez-Andres, M, Almeida, J, Martin-Ayuso, M, et al. Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment. Leukemia 2005;19:449–55.CrossRefGoogle ScholarPubMed
Rawstron, AC, Fenton, JA, Ashcroft, J, et al. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells. Blood 2000;96:3880–6.Google Scholar
Zent, CS, Wilson, CS, Tricot, G, et al. Oligoclonal protein bands and Ig isotype switching in multiple myeloma treated with high-dose therapy and hematopoietic cell transplantation. Blood 1998;91:3518–23.Google ScholarPubMed
Amara, S, Dezube, BJ, Cooley, TP, et al. HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients. Clin Infect Dis 2006;43:1198–205.CrossRefGoogle ScholarPubMed
Dezube, BJ, Aboulafia, DM, Pantanowitz, L. Plasma cell disorders in HIV-infected patients: from benign gammopathy to multiple myeloma. AIDS Reader 2004;14:372–4.Google ScholarPubMed
Passweg, J, Thiel, G, Bock, HA. Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients. Nephrol Dial Transplant 1996;11:2461–5.CrossRefGoogle ScholarPubMed
Fonseca, R, Barlogie, B, Bataille, R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004;64:1546–58.CrossRefGoogle ScholarPubMed
Kyle, RA, Rajkumar, SV. Multiple myeloma. N Engl J Med 2004;351:1860–73.CrossRefGoogle ScholarPubMed
Kuehl, WM, Bergsagel, PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175–87.CrossRefGoogle ScholarPubMed
Bergsagel, PL, Kuehl, WM. Chromosome translocations in multiple myeloma. Oncogene 2001;20:5611–22.CrossRefGoogle ScholarPubMed
Fonseca, R, Bailey, RJ, Ahmann, GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood 2002;100:1417–24.Google ScholarPubMed
Drach, J, Angerler, J, Schuster, J, et al. Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance. Blood 1995;86:3915–21.Google ScholarPubMed
Fonseca, R, Aguayo, P, Ahmann, GJ, et al. Translocations at 14q32 are common in patients with the monoclonal gammopathy of undetermined significance (MGUS) and involve several partner chromosomes. Blood 1999;94 Suppl 1:663a (A 2943).Google Scholar
Chng, WJ, Wier, SA, Ahmann, GJ, et al. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood 2005;106:2156–61.CrossRefGoogle ScholarPubMed
Magrangeas, F, Lode, L, Wuilleme, S, et al. Genetic heterogeneity in multiple myeloma. Leukemia 2005;19:191–4.CrossRefGoogle ScholarPubMed
Kaufmann, H, Ackermann, J, Baldia, C, et al. Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma. Leukemia 2004;18:1879–82.CrossRefGoogle Scholar
Hanamura, I, Stewart, JP, Huang, Y, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood 2006;108:1724–32.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Mesa, RA, Fonseca, R, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 2002;8:2210–16.Google ScholarPubMed
Galea, HR, Cogne, M. GM-CSF and IL-12 production by malignant plasma cells promotes cell-mediated immune responses against monoclonal Ig determinants in a light chain myeloma model. Clin Exp Immunol 2002;129:247–53.CrossRefGoogle Scholar
Vacca, A, Ria, R, Ribatti, D, et al. A paracrine loop in the vascular endothelial growth factor pathway triggers tumor angiogenesis and growth in multiple myeloma. Haematologica 2003;88:176–85.Google ScholarPubMed
Kumar, S, Fonseca, R, Dispenzieri, A, et al. Prognostic value of angiogenesis in solitary bone plasmacytoma. Blood 2003;101:1715–17.CrossRefGoogle ScholarPubMed
Kumar, S, Witzig, TE, Timm, M, et al. Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: Evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 2004;104:1159–65.CrossRefGoogle ScholarPubMed
Kumar, S, Witzig, TE, Timm, M, et al. Expression of VEGF and its receptors by myeloma cells. Leukemia 2003;17:2025–31.CrossRefGoogle ScholarPubMed
Vacca, A, Scavelli, C, Serini, G, et al. Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma. Blood 2006;108:1661–7.CrossRefGoogle ScholarPubMed
Kumar, S, Witzig, TE, Wellik, L, et al. Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Leukemia 2004;18:624–7.CrossRefGoogle Scholar
Cesana, C, Klersy, C, Barbarano, L, et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol 2002;20:1625–34.CrossRefGoogle ScholarPubMed
Kumar, S, Rajkumar, SV, Kyle, RA, et al. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol 2005;23:5668–74.CrossRefGoogle ScholarPubMed
Barosi, G, Boccadoro, M, Cavo, M, et al. Management of multiple myeloma and related-disorders: guidelines from the Italian Society of Hematology (SIE), Italian Society of Experimental Hematology (SIES) and Italian Group for Bone Marrow Transplantation (GITMO). Haematologica 2004;89:717–41.Google Scholar
,The International Myeloma Working Group.Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749–57.CrossRefGoogle Scholar
Rajkumar, SV, Dispenzieri, A, Fonseca, R, et al. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia 2001;15:1274–6.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Moulopoulos, , Maniatis, A, et al. Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood 2000;96:2037–44.Google ScholarPubMed
Ross, FM, Ibrahim, AH, Vilain-Holmes, A, et al. Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma. Leukemia 2005;19:1634–42.CrossRefGoogle Scholar
Wang, M, Alexanian, R, Delasalle, K, et al. Abnormal MRI of spine is the dominant risk factor for early progression of asymptomatic multiple myeloma. Blood 2003;102:687a.Google Scholar
Witzig, TE, Kyle, RA, O'Fallon, WM, Greipp, PR. Detection of peripheral blood plasma cells as a predictor of disease course in patients with smoldering multiple myeloma. Br J Haematol 1994;87:266–72.CrossRefGoogle Scholar
Kyle, R, Remstein, E, Therneau, T, et al. The natural history of smoldering (asymptomatic) multiple myeloma. Blood 2005;106:949a (A3396).Google Scholar
Weber, D, Wang, LM, Delasalle, K, et al. Risk factors for early progression of asymptomatic multiple myeloma. Hematol J 2003;4 Suppl 1:S31.Google Scholar
Hjorth, M, Hellquist, L, Holmberg, E, et al. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I–a randomized study. Myeloma Group of Western Sweden. Eur J Haematol 1993;50:95–102.CrossRefGoogle ScholarPubMed
Riccardi, A, Mora, O, Tinelli, C, et al. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma. Br J Cancer 2000;82:1254–60.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Gertz, MA, Lacy, MQ, et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia 2003;17:775–9.CrossRefGoogle ScholarPubMed
Weber, DM, Gavino, M, Delasalle, K, et al. Thalidomide alone or with dexamethasone for multiple myeloma. Blood 1999;94 Suppl 1:604a (A2686).Google Scholar
Bruno, B, Giaccone, L, Rotta, M, et al. Novel targeted drugs for the treatment of multiple myeloma: from bench to bedside. Leukemia 2005;19:1729–38.CrossRefGoogle ScholarPubMed
Richardson, PG, Mitsiades, CS, Hideshima, T, et al. Novel biological therapies for the treatment of multiple myeloma. Best Pract Res Clin Hematol 2005;18:619–34.CrossRefGoogle ScholarPubMed
Kumar, S, Raje, N, Hideshima, T, et al. Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs. Leukemia 2005;19:1253–61.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Kyle, RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2005;80:1371–82.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Incidence of multiple myeloma in Olmsted County, Minnesota: trend over 6 decades. Cancer 2004;101:2667–74.CrossRefGoogle ScholarPubMed
Jemal, A, Siegel, R, Ward, E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66.CrossRefGoogle ScholarPubMed
Kyle, RA, Gertz, MA, Witzig, TE, et al. Review of 1,027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proc 2003;78:21–33.CrossRefGoogle Scholar
Roodman, GD. Role of the bone marrow microenvironment in multiple myeloma. J Bone Miner Res 2002;17:1921–5.CrossRefGoogle ScholarPubMed
Roodman, GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–64.CrossRefGoogle ScholarPubMed
Tian, E, Zhan, F, Walker, R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349:2483–94.CrossRefGoogle ScholarPubMed
Kyle, RA. Long-term survival in multiple myeloma. N Engl J Med 1983;308:314–16.CrossRefGoogle ScholarPubMed
Attal, M, Payen, C, Facon, T, et al. Single versus double transplant in myeloma: a randomized trial of the “Inter Groupe Francais du Myelome” (IFM). Blood 1997;90 Suppl 1:418a.Google Scholar
Barlogie, B, Jagannath, S, Desikan, KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999;93:55–65.Google ScholarPubMed
Desikan, R, Barlogie, B, Sawyer, J, et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000;95:4008–10.Google ScholarPubMed
Durie, BG, Salmon, SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36:842–54.3.0.CO;2-U>CrossRefGoogle Scholar
Kyle, RA. Prognostic factors in multiple myeloma. Stem Cells 1995;2:56–63.Google Scholar
Rapoport, BL, Falkson, HC, Falkson, G. Prognostic factors affecting the survival of patients with multiple myeloma. A retrospective analysis of 86 patients. S Afr Med J 1990;79:65–7.Google Scholar
Greipp, PR, San Miguel, JF, Durie, BG, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412–20.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Greipp, PR. Prognostic factors in multiple myeloma. Hematol Oncol Clin North Am 1999;13:1295–314.CrossRefGoogle ScholarPubMed
Tricot, G, Sawyer, JR, Jagannath, S, et al. Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants. J Clin Oncol 1997;15:2659–66.CrossRefGoogle ScholarPubMed
Greipp, PR. Prognosis in myeloma. [75 refs]. Mayo Clin Proc 1994;69:895–902.CrossRefGoogle Scholar
Facon, T, Avet-Loiseau, H, Guillerm, G, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001;97:1566–71.CrossRefGoogle ScholarPubMed
Greipp, PR, Leong, T, Bennett, JM, et al. Plasmablastic morphology–an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. Blood 1998;91:2501–7.Google Scholar
Greipp, PR, Lust, JA, O'Fallon, WM, et al. Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma [see comments]. Blood 1993;81:3382–7.Google Scholar
Singhal, S, Mehta, J, Desikan, R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565–71.CrossRefGoogle ScholarPubMed
Richardson, PG, Barlogie, B, Berenson, J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348:2609–17.CrossRefGoogle ScholarPubMed
Richardson, PG, Sonneveld, P, Schuster, MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487–98.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Hayman, SR, Lacy, MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050–3.CrossRefGoogle ScholarPubMed
Richardson, PG, Blood, E, Mitsiades, CS, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006;108:3458–64.CrossRefGoogle ScholarPubMed
Dispenzieri, A, Rajkumar, SV, Gertz, MA, et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Proc 2007;82:323–41.CrossRefGoogle ScholarPubMed
Durie, BGM, Harousseau, J-L, Miguel, JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.CrossRefGoogle ScholarPubMed
Cavo, M, Zamagni, E, Tosi, P, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005;106:35–9.CrossRefGoogle ScholarPubMed
Fermand, J-P, Jaccard, A, Macro, M, et al. A randomized comparison of dexamethasone + thalidomide (Dex/Thal) vs dex + placebo (Dex/P) in patients (pts) with relapsing multiple myeloma (MM). Blood 2006;108:3563–.Google Scholar
Rajkumar, SV, Blood, E, Vesole, DH, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006;24:431–6.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Hussein, M, Catalano, J, et al. A randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as primary therapy for newly diagnosed multiple myeloma. Blood 2006;108:795.Google Scholar
Rajkumar, SV, Rosiñol, L, Hussein, M, et al. A multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone versus dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008;26:2171–7.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Hayman, S, Gertz, MA, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002;20:4319–23.CrossRefGoogle ScholarPubMed
Cavo, M, Zamagni, E, Tosi, P, et al. First-line therapy with thalidomide and dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica 2004;89:826–31.Google ScholarPubMed
Lacy, MQ, Gertz, MA, Dispenzieri, AA, et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007;82:1179–84.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Jacobus, S, Callander, N, et al. A randomized phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. Blood 2006;108:799.Google Scholar
Kumar, S, Dispenzieri, A, Lacy, MQ, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007;21:2035–42.CrossRefGoogle ScholarPubMed
Mazumder, A, Kaufman, J, Niesvizky, R, et al. Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia 2008;22:1280–1; author reply 1281–2.CrossRefGoogle ScholarPubMed
Richardson, PG, Chanan-Khan, A, Schlossman, RL, et al. Phase II trial of single agent bortezomib (VELCADE®) in patients with previously untreated multiple myeloma (MM). Blood 2004;104:100a (A336).Google Scholar
Jagannath, S, Durie, BG, Wolf, J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005;129:776–83.CrossRefGoogle ScholarPubMed
Harousseau, J, Attal, M, Leleu, X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 2006;91:1498–505.Google ScholarPubMed
Harousseau, J-L, Marit, G, Caillot, D, et al. VELCADE/dexamethasone (Vel/Dex) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): an interim analysis of the IFM 2005-01 randomized multicenter phase III trial. Blood 2006;108:56.Google Scholar
San-Miguel, J, Harousseau, JL, Joshua, D, et al. Individualizing treatment of patients with myeloma in the era of novel agents. J Clin Oncol 2008;26:2761–6.CrossRefGoogle ScholarPubMed
Kyle, RA, Rajkumar, SV. Multiple myeloma. Blood 2008;111:2962–72.CrossRefGoogle ScholarPubMed
,Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998;16:3832–42.CrossRefGoogle Scholar
Facon, T, Mary, JY, Hulin, C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007;370:1209–18.CrossRefGoogle ScholarPubMed
Hulin, C, Facon, T, Rodon, P, et al. Melphalan-prednisone-thalidomide (MP-T) demonstrates a significant survival advantage in elderly patients ≥ 75 years with multiple myeloma compared with melphalan-prednisone (MP) in a randomized, double-blind, placebo-controlled trial, IFM 01/01. ASH Annual Meeting Abstracts 2007;110:75.Google Scholar
Waage, A, Gimsing, P, Juliusson, G, et al. Melphalan-prednisone-thalidomide to newly diagnosed patients with multiple myeloma: a placebo controlled randomised phase 3 trial. ASH Annual Meeting Abstracts 2007;110:78.Google Scholar
Facon, T, Mary, JY, Hulin, C, et al. Major superiority of melphalan–prednisone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma. Blood 2005;106:230a (A780).Google Scholar
Palumbo, A, Bringhen, S, Caravita, T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367:825–31.CrossRefGoogle ScholarPubMed
Mateos, M-V, Hernandez, J-M, Hernandez, M-T, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006;108:2165–72.CrossRefGoogle ScholarPubMed
San Miguel, JF, Schlag, R, Khuageva, NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906–17.CrossRefGoogle ScholarPubMed
Palumbo, A, Falco, P, Corradini, P, et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA Italian Multiple Myeloma Network. J Clin Oncol 2007;25:4459–65.CrossRefGoogle ScholarPubMed
Attal, M, Harousseau, JL, Stoppa, AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996;335:91–7.CrossRefGoogle ScholarPubMed
Child, JA, Morgan, GJ, Davies, FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348:1875–83.CrossRefGoogle ScholarPubMed
Blade, J, Vesole, DH, Gertz, M. Transplantation for multiple myeloma: who, when, how often?Blood 2003;102:3469–77.CrossRefGoogle Scholar
Kumar, A, Loughran, T, Alsina, M, et al. Management of multiple myeloma: a systematic review and critical appraisal of published studies. Lancet Oncol 2003;4:293–304.CrossRefGoogle ScholarPubMed
Moreau, P, Facon, T, Attal, M, et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 2002;99:731–5.CrossRefGoogle Scholar
Bensinger, W, Giralt, S, Holmberg, L, et al. 166H0-DOTMP and high-dose melphalan before autologous peripheral blood stem cell transplantation in patients with multiple myeloma. Hematol J 2003;4 Suppl 1:S215–16.Google Scholar
Dispenzieri, A, Wiseman, GA, Lacy, MQ, et al. A phase II study of high dose 153-samarium EDMTP (153-Sm EDMTP) and melphalan for peripheral stem cell transplantation (PBSCT) in multiple myeloma (MM). Blood 2003;102:982a.Google Scholar
Fermand, JP, Ravaud, P, Chevret, S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998;92:3131–6.Google ScholarPubMed
Facon, T, Mary, JY, Harousseau, JL, et al. Front-line or rescue autologous bone marrow transplantation (ABMT) following a first course of high dose melphalan (HDM) in multiple myeloma (MM). Preliminary results of a prospective randomized trial (CIAM) protocol. Blood 1996;88 Suppl 1:685a.Google Scholar
Barlogie, B, Kyle, R, Anderson, K, et al. Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m2 + TBI 12 Gy autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: results of Intergroup Trial S9321. Blood 2003;102:42a.Google Scholar
Blade, J, Sureda, A, Ribera, JM, et al. High-dose therapy autotransplantation/intensification versus continued conventional chemotherapy in multiple myeloma patients responding to initial chemotherapy. Definitive results from PETHEMA after a median follow-up of 66 months. Blood 2003;102:42a.Google Scholar
Rajkumar, SV, Fonseca, R, Lacy, MQ, et al. Autologous stem cell transplantation for relapsed and primary refractory myeloma. Bone Marrow Transplant 1999;23:1267–72.CrossRefGoogle ScholarPubMed
Blade, J, Esteve, J. Treatment approaches for relapsing and refractory multiple myeloma. [44 refs]. Acta Oncologica 2000;39:843–7.Google Scholar
Barlogie, B, Jagannath, S, Vesole, DH, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997;89:789–93.Google ScholarPubMed
Attal, M, Harousseau, JL, Facon, T, et al. Double autologous transplantation improves survival of multiple myeloma patients: final analysis of a prospective randomized study of the “Intergroupe Francophone du Myelome” (IFM 94). Blood 2002;100:5a.Google Scholar
Cavo, M, Cellini, C, Zamagni, E, et al. Superiority of double over single autologous stem cell transplantation as first-line therapy for multiple myeloma. Blood 2004;104:155a (A536).Google Scholar
Fermand, JP, Alberti, C, Marolleau, JP. Single versus tandem high dose therapy (HDT) supported with autologous blood stem cell (ABSC) transplantation using unselected or CD34-enriched ABSC: results of a two by two designed randomized trial in 230 young patients with multiple myeloma (MM). Hematol J 2003;4 Suppl 1:S59.Google Scholar
Goldschmidt, H. Single vs. tandem autologous transplantation in multiple myeloma: the GMMG experience. Hematol J 2003;4 Suppl 1:S61.Google Scholar
Sirohi, B, Powles, R, Singhal, S, et al. High-dose melphalan and second autografts for myeloma relapsing after one autograft: results equivalent to tandem autotransplantation. Blood 2001;98:402a (A1690).Google Scholar
Mehta, J, Singhal, S. Graft-versus-myeloma. Bone Marrow Transplant 1998;22:835–43.CrossRefGoogle ScholarPubMed
Gahrton, G, Svensson, H, Cavo, M, et al. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–93 and 1994–8 at European Group for Blood and Marrow Transplantation centres. Br J Haematol 2001;113:209–16.CrossRefGoogle Scholar
Einsele, H, Schafer, HJ, Hebart, H, et al. Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning. Br J Haematol 2003;121:411–18.CrossRefGoogle ScholarPubMed
Crawley, C, Lalancette, M, Szydlo, R, et al. Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood 2005;105:4532–9.CrossRefGoogle ScholarPubMed
Maloney, DG, Molina, AJ, Sahebi, F, et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003;102:3447–54.CrossRefGoogle ScholarPubMed
Garban, F, Attal, M, Michallet, M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood 2006;107:3474–80.CrossRefGoogle Scholar
Jagannath, S, Richardson, PG, Sonneveld, P, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2006;21:151–7.CrossRefGoogle ScholarPubMed
Sagaster, V, Ludwig, H, Kaufmann, H, et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 2006;21:164–8.CrossRefGoogle ScholarPubMed
Myeloma Trialists' Collaborative, Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol 2001;113:1020–34.CrossRefGoogle Scholar
Barlogie, B, Kyle, RA, Anderson, KC, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol 2006;24:929–36.CrossRefGoogle ScholarPubMed
Berenson, JR, Crowley, JJ, Grogan, TM, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 2002;99:3163–8.CrossRefGoogle ScholarPubMed
Attal, M, Harousseau, J-L, Leyvraz, S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006;108:3289–94.CrossRefGoogle ScholarPubMed
Abdelkefi, A, Ladeb, S, Torjman, L, et al. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood 2008;111:1805–10.CrossRefGoogle ScholarPubMed
Gertz, MA, Lacy, MQ, Inwards, DJ, et al. Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma. Bone Marrow Transplant 1999;23:221–6.CrossRefGoogle ScholarPubMed
Alexanian, R, Barlogie, B, Dixon, D. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med 1986;105:8–11.CrossRefGoogle ScholarPubMed
Gertz, MA, Garton, JP, Greipp, PR, et al. A phase II study of high-dose methylprednisolone in refractory or relapsed multiple myeloma. Leukemia 1995;9:2115–18.Google ScholarPubMed
Barlogie, B, Spencer, T, Tricot, G, et al. Long term follow up of 169 patients receiving a phase II trial of single agent thalidomide for advanced and refractory multiple myeloma (MM). Blood 2000;96:514a (A2213).Google Scholar
Dimopoulos, MA, Anagnostopoulos, A, Weber, D. Treatment of plasma cell dyscrasias with thalidomide and its derivatives. J Clin Oncol 2003;21:4444–54.CrossRefGoogle ScholarPubMed
Kumar, S, Witzig, TE, Rajkumar, SV. Thalidomide – current role in the treatment of non-plasma cell malignancies. J Clin Oncol 2004;22:2477–88.CrossRefGoogle ScholarPubMed
Richardson, P, Schlossman, R, Jagannath, S, et al. Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity. Mayo Clin Proc 2004;79:875–82.CrossRefGoogle ScholarPubMed
Kumar, S, Gertz, MA, Dispenzieri, A, et al. Response rate, durability of response, and survival after thalidomide therapy for relapsed multiple myeloma.[comment]. Mayo Clin Proc 2003;78:34–9.CrossRefGoogle Scholar
Juliusson, G, Celsing, F, Turesson, I, et al. Thalidomide frequently induces good partial remission and best response ever in patients with advanced multiple myeloma and prior high dose melphalan and autotransplant. Blood 1999;94 Suppl 1:124a (A546).Google Scholar
Anagnostopoulos, A, Weber, D, Rankin, K, et al. Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003;121:768–71.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Hamilos, G, Zomas, A, et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J 2004;5:112–17.CrossRefGoogle ScholarPubMed
Garcia-Sanz, R, Gonzalez-Fraile, MI, Sierra, M, et al. The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/refractory multiple myeloma. Hematol J 2002;3:43–8.CrossRefGoogle ScholarPubMed
Kropff, MH, Lang, N, Bisping, G, et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol 2003;122:607–16.CrossRefGoogle ScholarPubMed
Coleman, M, Leonard, J, Lyons, L, et al. BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenstrom's macroglobulinemia. Leuk Lymphoma 2002;43:1777–82.CrossRefGoogle ScholarPubMed
Adams, J. Proteasome inhibitors as new anticancer drugs. Curr Opin Oncol 2002;14:628–34.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Richardson, PG, Hideshima, T, et al. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2004;23:630–9.CrossRefGoogle Scholar
Berenson, JR, Jagannath, S, Barlogie, B, et al. Experience with long-term therapy using the proteasome inhibitor, bortezomib, in advanced multiple myeloma (MM). Proc Am Soc Clin Oncol 2003;22:581.Google Scholar
Richardson, PG, Sonneveld, P, Schuster, M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110:3557–60.CrossRefGoogle ScholarPubMed
Orlowski, RZ, Voorhees, PM, Garcia, R, et al. Phase I study of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with refractory hematologic malignancies. Proc Am Soc Clin Oncol 2003;22:200.Google Scholar
Orlowski, RZ, Zhuang, SH, Parekh, T, et al. The DOXIL-MMY-3001 Study Investigators. The combination of pegylated liposomal doxorubicin and bortezomib significantly improves time to progression of patients with relapsed/refractory multiple myeloma compared with bortezomib alone: results from a planned interim analysis of a randomized phase III study. ASH Annual Meeting Abstracts 2006;108:404.Google Scholar
Zangari, M, Barlogie, B, Burns, MJ, et al. Velcade (V)-thalidomide (T)-dexamethasone (D) for advanced and refractory multiple myeloma (MM): long-term follow-up of phase I-II trial UARK 2001-37: superior outcome in patients with normal cytogenetics and no prior T. ASH Annual Meeting Abstracts 2005;106:2552.Google Scholar
Zangari, M, Tricot, G, Zeldis, J, et al. Results of phase I study of CC-5013 for the treatment of multiple myeloma (MM) patients who relapse after high dose chemotherapy (HDCT). Blood 2001:775a (A3226).
Richardson, PG, Schlossman, RL, Weller, E, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100:3063–7.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Spencer, A, Attal, M, et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010). Blood 2005;106:6.Google Scholar
Weber, DM, Chen, C, Niesvizky, R, et al. Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of a North American phase III study (MM-009). Proc Am Soc Clin Oncol 2006;24:A7521.Google Scholar
Hideshima, T, Chauhan, D, Podar, K, et al. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin Oncol 2001;28:607–12.CrossRefGoogle ScholarPubMed
Munshi, NC. Arsenic trioxide: an emerging therapy for multiple myeloma. Oncologist 2001;6 Suppl 2:17–21.CrossRefGoogle ScholarPubMed
Streetly, M, Jones, RW, Knight, R, et al. An update of the use and outcomes of the new immunomodulatory agent CC-4047 (actimid) in patients with relapsed/refractory myeloma. Blood 2003;102:236a.Google Scholar
Gucalp, R, Theriault, R, Gill, I, et al. Treatment of cancer-associated hypercalcemia. Double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone. Arch Intern Med 1994;154:1935–44.CrossRefGoogle ScholarPubMed
Major, P, Lortholary, A, Hon, J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19:558–67.CrossRefGoogle ScholarPubMed
Berenson, JR, Lichtenstein, A, Porter, L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. [see comments]. N Engl J Med 1996;334:488–93.CrossRefGoogle Scholar
Berenson, JR, Rosen, LS, Howell, A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. [Erratum appears in Cancer 2001 May 15;91(10):1956.] Cancer 2001;91:1191–200.3.0.CO;2-0>CrossRefGoogle Scholar
Rosen, LS, Gordon, D, Kaminski, M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase II, double blind, comparative trial. Cancer J 2001;7:377–87.Google ScholarPubMed
Berenson, JR, Hillner, BE, Kyle, RA, et al. American Society of Clinical Oncology Clinical Practice Guidelines: The role of bisphosphonates in multiple myeloma. J Clin Oncol 2002;20:3719–36.CrossRefGoogle Scholar
Marx, RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic.[see comment]. J Oral Maxillofac Surg 2003;61:1115–17.CrossRefGoogle Scholar
Kademani, D, Koka, S, Lacy, MQ, et al. Primary surgical therapy for osteonecrosis of the jaw secondary to bisphosphonate therapy. Mayo Clin Proc 2006;81:1100–3.CrossRefGoogle ScholarPubMed
Badros, A, Weikel, D, Salama, A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006;24:945–52.CrossRefGoogle ScholarPubMed
Durie, BG, Katz, M, Crowley, J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005;353:99–102; discussion 99–102.Google ScholarPubMed
Ruggiero, SL, Mehrotra, B, Rosenberg, TJ, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527–34.CrossRefGoogle ScholarPubMed
Lacy, MQ, Dispenzieri, A, Gertz, MA, et al. Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc 2006;81:1047–53.CrossRefGoogle Scholar
Dimopoulos, MA, Kastritis, E, Anagnostopoulos, A, et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006;91:968–71.Google ScholarPubMed
Melton, LJ, Kyle, RA, Achenbach, SJ, et al. Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 2005;20:487–93.CrossRefGoogle ScholarPubMed
Miller, PD. Treatment of osteoporosis in chronic kidney disease and end-stage renal disease. Curr Osteoporos Rep 2005;3:5–12.CrossRefGoogle ScholarPubMed
Fourney, DR, Schomer, DF, Nader, R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg 2003;98:21–30.Google ScholarPubMed
Yussim, E, Schwartz, E, Sidi, Y, et al. Acute renal failure precipitated by non-steroidal anti-inflammatory drugs (NSAIDs) in multiple myeloma. Am J Hematol 1998;58:142–4.3.0.CO;2-D>CrossRefGoogle Scholar
Wu, MJ, Kumar, KS, Kulkarni, G, et al. Multiple myeloma in naproxen-induced acute renal failure. N Engl J Med 1987;317:170–1.Google ScholarPubMed
Johnson, WJ, Kyle, RA, Pineda, AA, et al. Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy. Arch Intern Med 1990;150:863–9.CrossRefGoogle ScholarPubMed
Garton, JP, Gertz, MA, Witzig, TE, et al. Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective, randomized, placebo-controlled, double-blind trial. Arch Intern Med 1995;155:2069–74.CrossRefGoogle ScholarPubMed
Dammacco, F, Castoldi, G, Rodjer, S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma.[Erratum appears inBr J Haematol 2001 Sep;114(3):738.] Br J Haematol 2001;113:172–9.Google Scholar
Oken, MM, Pomeroy, C, Weisdorf, D, et al. Prophylactic antibiotics for the prevention of early infection in multiple myeloma. Am J Med 1996;100:624–8.CrossRefGoogle ScholarPubMed
Gertz, MA, Kyle, RA. Hyperviscosity syndrome. J Intensive Care Med 1995;10:128–41.CrossRefGoogle ScholarPubMed
Weber, D, Rankin, K, Gavino, M, et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003;21:16–19.CrossRefGoogle ScholarPubMed
Barlogie, B, Desikan, R, Eddlemon, P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001;98:492–4.CrossRefGoogle Scholar
Palumbo, A, Rajkumar, SV, Dimopoulos, MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414–23.CrossRefGoogle Scholar
Osman, K, Comenzo, R, Rajkumar, SV. Deep vein thrombosis and thalidomide therapy for multiple myeloma. N Engl J Med 2001;344:1951–2.CrossRefGoogle ScholarPubMed
Zangari, M, Anaissie, E, Barlogie, B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001;98:1614–15.CrossRefGoogle ScholarPubMed
Zangari, M, Siegel, E, Barlogie, B, et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002;100:1168–71.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Blood, E. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med 2006;354:2079–80.Google ScholarPubMed
Zeldis, JB, Williams, BA, Thomas, SD, et al. S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide. Clin Ther 1999;21:319–30.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Gertz, MA, Witzig, TE. Life-threatening toxic epidermal necrolysis with thalidomide therapy for myeloma. N Engl J Med 2000;343:972–3.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Eleutherakis-Papaiakovou, V. Adverse effects of thalidomide administration in patients with neoplastic diseases. Am J Med 2004;117:508–15.CrossRefGoogle ScholarPubMed
Badros, AZ, Siegel, E, Bodenner, D, et al. Hypothyroidism in patients with multiple myeloma following treatment with thalidomide. Am J Med 2002;112:412–13.CrossRefGoogle ScholarPubMed
Menon, S, Habermann, T, Witzig, T. Lenalidomide-associated hypothyroidism. Leuk Lymphoma 2007;48:2465–7.CrossRefGoogle ScholarPubMed
Stein, EM, Rivera, C. Transient thyroiditis after treatment with lenalidomide in a patient with metastatic renal cell carcinoma. Thyroid 2007;17:681–3.CrossRefGoogle Scholar
Kastritis, E, Dimopoulos, MA. Thalidomide in the treatment of multiple myeloma. Best Pract Res Clin Haematol 2007;20:681–99.CrossRefGoogle ScholarPubMed
Eriksson, T, Hoglund, P, Turesson, I, et al. Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. J Pharm Pharmacol 2003;55:1701–6.CrossRefGoogle ScholarPubMed
Chen, N, Lau, H, Kong, L, et al. Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol 2007;47:1466–75.CrossRefGoogle ScholarPubMed
Gramont, A, Grosbois, B, Michaux, JL, et al. Myelome a IgM: 6 observations et revue de la litterature. Rev Med Interne 1990;11:13–18.CrossRefGoogle Scholar
Mansoor, A, Medeiros, LJ, Weber, DM, et al. Cytogenetic findings in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course. Am J Clin Pathol 2001;116:543–9.CrossRefGoogle ScholarPubMed
Wong, KF, So, CC. Waldenstrom macroglobulinemia with karyotypic aberrations involving both homologous 6q. Cancer Genet Cytogenet 2001;124:137–9.CrossRefGoogle ScholarPubMed
Jankovic, GM, Colovic, MD, Wiernik, PH, et al. Multiple karyotypic aberrations in a polymorphous variant of Waldenstrom macroglobulinemia. Cancer Genet Cytogenet 1999;111:77–80.CrossRefGoogle Scholar
Schop, RF, Jalal, SM, Wier, SA, et al. Deletions of 17p13.1 and 13q14 are uncommon in Waldenstrom macroglobulinemia clonal cells and mostly seen at the time of disease progression. Cancer Genet Cytogenet 2002;132:55–60.CrossRefGoogle Scholar
Avet-Loiseau, H, Garand, R, Lode, L, et al. 14q32 translocations discriminate IgM multiple myeloma from Waldenstrom's macroglobulinemia. Semin Oncol 2003;30:153–5.CrossRefGoogle ScholarPubMed
Blade, J, Kyle, RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol Oncol Clin North Am 1999;13:1259–72.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Palumbo, A, Delasalle, KB, et al. Primary plasma cell leukaemia. Br J Haematol 1994;88:754–9.CrossRefGoogle ScholarPubMed
Tiedemann, RE, Gonzalez-Paz, N, Kyle, RA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008;22:1044–52.CrossRefGoogle ScholarPubMed
Garcia-Sanz, R, Orfao, A, Gonzalez, M, et al. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood 1999;93:1032–7.Google ScholarPubMed
Avet-Loiseau, H, Gerson, F, Magrangeas, F, et al. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood 2001;98:3082–6.CrossRefGoogle ScholarPubMed
Saez, B, Martin-Subero, JI, Guillen-Grima, F, et al. Chromosomal abnormalities clustering in multiple myeloma reveals cytogenetic subgroups with nonrandom acquisition of chromosomal changes. Leukemia 2004;18:654–7.CrossRefGoogle ScholarPubMed
Smadja, NV, Bastard, C, Brigaudeau, C, et al. Groupe Francais de Cytogenetique Hématologique. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001;98:2229–38.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Kyle, RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2005;80:1371–82.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 2003;102:3759–64.CrossRefGoogle ScholarPubMed
Gobbi, PG, Baldini, L, Broglia, C, et al. Prognostic validation of the international classification of immunoglobulin M gammopathies: a survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance?Clin Cancer Res 2005;11:1786–90.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Semin Oncol 2003;30:169–71.CrossRefGoogle ScholarPubMed
Baldini, L, Goldaniga, M, Guffanti, A, et al. Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. J Clin Oncol 2005;23:4662–8.CrossRefGoogle ScholarPubMed
Owen, RG, Treon, SP, Al-Katib, A, et al. Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003;30:110–15.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Kiamouris, C, Moulopoulos, . Solitary plasmacytoma of bone and extramedullary plasmacytoma. Hematol Oncol Clin North Am 1999;13:1249–57.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Dispenzieri, A, Kyle, RA. Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc 2006;81:693–703.CrossRefGoogle ScholarPubMed
Dispenzieri, A, Kyle, RA, Lacy, MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101:2496–506.CrossRefGoogle ScholarPubMed
Wang, M, Delasalle, K, Giralt, S, et al. Rapid control of previously untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy. Blood 2005;106:784.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×